The G protein-coupled receptor GPR54 (AXOR12, OT7T175) is central to acquisition of reproductive competency in mammals. Peptide ligands (kisspeptins) for this are encoded by the Kiss1 gene, and administration exogenous kisspeptins stimulates hypothalamic gonadotropin-releasing hormone (GnRH) release several species, including humans. To establish that authentic agonists vivo determine whether these have additional physiological functions we generated mice with a targeted disruption gene....

Kisspeptin and its receptor GPR54 have recently been identified as key signaling partners in the neural control of fertility animal models humans. The gonadotropin-releasing hormone (GnRH) neurons represent final output network controlling are suspected to be primary locus kisspeptin–GPR54 signaling. Using mouse models, present study addressed whether kisspeptin a role activation GnRH generate luteinizing (LH) surge responsible for ovulation. Dual-label immunocytochemistry experiments showed...

Kisspeptin-GPR54 signalling is essential for normal reproductive functioning. However, the distribution of kisspeptin neuronal cell bodies and their projections not well established. The present study aimed to provide a detailed account neuroanatomy in mouse brain. Using polyclonal rabbit antibody AC566, directed towards final ten C-terminal amino acids murine kisspeptin, three populations kisspeptin-expressing were identified adult female One exists as dense periventricular continuum cells...

Kisspeptin and G protein-coupled receptor 54 (GPR54) are now acknowledged to play essential roles in the neural regulation of fertility. Using a transgenic Gpr54 LacZ knock-in mouse model, this study aimed provide 1) detailed map cells expressing brain 2) an analysis expression GnRH neurons across postnatal development. The highest density Gpr54-expressing central nervous system was found dentate gyrus hippocampus beginning on d 6 (P6). Abundant also noted septum, rostral preoptic area...

The G protein-coupled receptor GPR54, and its peptide ligand kisspeptin (Kp), are crucial for the induction maintenance of mammalian reproductive function. GPR54 is expressed by GnRH neurons directly activated Kp to stimulate release. We hypothesized that may be able act at nerve terminals located in mediobasal hypothalamus (MBH) region. To test this hypothesis, we used organotypic culture MBH explants challenged with Kp, followed RIA detect released into cultured medium. stimulation 1 h...

The transition to puberty and adult fertility both require a minimum level of energy availability. adipocyte-derived hormone leptin signals the long-term status peripheral stores serves as key metabolic messenger neuroendocrine reproductive axis. Humans mice lacking or its receptor fail complete are infertile. Restoration levels in these individuals promotes sexual maturation, which requires pulsatile, coordinated delivery gonadotropin-releasing pituitary resulting surge luteinizing (LH);...

The anteroventral periventricular nucleus (AVPV) is thought to play a key role in regulating the excitability of gonadotropin-releasing hormone (GnRH) neurons that control fertility. Using an angled, parahorizontal brain slice preparation we have undertaken series electrophysiological experiments examine how AVPV controls GnRH adult male and female mice. More than half (59%) located rostral preoptic area were found receive monosynaptic inputs from sex-dependent manner. stimulation...

Reproduction is controlled in the brain by a neural network that drives secretion of gonadotropin-releasing hormone (GnRH). Various permissive homeostatic signals must be integrated to achieve ovulation mammals. However, events controlling timely activation GnRH neurons are not completely understood. Here we show kisspeptin, potent activator neuronal activity, directly communicates with synthesize gaseous transmitter nitric oxide (NO) preoptic region coordinate progression ovarian cycle....

Abstract It is now well established that the kisspeptin neurons of hypothalamus play a key role in regulating activity gonadotropin‐releasing hormone (GnRH) neurons. The population residing rostral periventricular region third ventricle (RP3V), encompassing anteroventral (AVPV) and preoptic nuclei (PVpo), are implicated generation preovulatory GnRH surge mechanism puberty onset female rodents. present study examined whether these may express other neuropeptides adult mouse. Initially,...

In the ever-changing physiological context of neuroendocrine brain, mechanisms by which cellular events involving neurons, astroglia, and vascular cells are coordinated to bring forth appropriate neuronal signaling is not yet known but amenable examination. median eminence hypothalamus, endothelial key players in plasticity tanycytes (specialized astroglia) synapse efficacy. Here we report that estradiol acts on both purified isolated trigger endothelial-to-glial communication leads a sudden...

NMDA and kisspeptins can stimulate gonadotropin-releasing hormone (GnRH) release after peripheral or central administration in mice. To determine whether these agonists act independently through a common pathway, we have examined their ability to GnRH/luteinizing (LH) Kiss1- Gpr54 (Kiss1r)-null mutant Peripheral injection of failed GnRH/LH prepubertal gonadally intact male Dual-labeling experiments indicated direct activation Kiss1-expressing neurons the arcuate nucleus. In contrast, into...

Kisspeptins regulate the mammalian reproductive axis by stimulating release of gonadotrophin releasing hormone (GnRH). Different length kisspeptins (KP) are found 54, 14, 13 or 10 amino-acids which share a common C-terminal 10-amino acid sequence. KP-54 and KP-10 have been widely used to stimulate but data suggest that not equally effective at eliciting secretion after peripheral delivery. To confirm this, we analysed effect systemic administration on luteinizing (LH) into bloodstream male...

Considerable research has been devoted to the understanding of how nitric oxide (NO) influences brain function. Few studies, however, have addressed its production is physiologically regulated. Here, we report that protein–protein interactions between neuronal NO synthase (nNOS) and glutamate NMDA receptors via scaffolding protein postsynaptic density-95 (PSD-95) in hypothalamic preoptic region adult female rats sensitive cyclic estrogen fluctuation. Coimmunoprecipitation experiments were...

Background Mll5 is currently a member of the Mll family SET domain histone methyltransferase proteins but studies have also showed that it could be part SET3 branch proteins. Recently, constitutive knock out animal shown required for proper haematopoietic stem cell differentiation, and loss results in synthetic lethality genome de-methylation. deficient male mice are infertile here we analyse consequences deficiency spermatogenesis. Methodology/Principal Findings mice, not female infertile....

Abstract Estrogens and nitric oxide (NO) exert wide‐ranging effects on brain function. Recent evidence suggested that one important mechanism for the regulation of NO production may reside in differential coupling calcium‐activated neuronal synthase (nNOS) to glutamate NMDA receptor channels harboring NR2B subunits by scaffolding protein post‐synaptic density‐95 (PSD‐95), estrogens promote formation this ternary complex. Here, we demonstrate 30‐min estradiol‐treatment triggers physically...

Within the preoptic region, nitric oxide (NO) production varies during ovarian cycle and has ability to impact hypothalamic reproductive function. One mechanism for regulation of NO release mediated by estrogens estrous includes physical association calcium-activated neuronal synthase (nNOS) enzyme with glutamate N-methyl-d-aspartate (NMDA) receptor channels via postsynaptic density 95 scaffolding protein. Here we demonstrate that endogenous variations in levels also coincide corresponding...

Kisspeptins, the ligands of kisspeptin receptor known for its roles in reproduction and cancer, are also vasoconstrictor peptides atherosclerosis-prone human aorta coronary artery. The aim this study was to further investigate cardiovascular localisation function kisspeptins their compared rat mouse heart. Immunohistochemistry radioligand binding techniques were employed localisation, density pharmacological characteristics cardiac tissues from all three species. Radioimmunoassay used detect...

Abstract: Chronic hypoxemia, as evidenced in de-acclimatized high-altitude residents or patients with chronic obstructive respiratory disorders, is a common medical condition that can produce serious neurological alterations. However, the pathogenesis of this phenomenon unknown. We have found adult rodents exposed for several days/weeks to hypoxia, an arterial oxygen tension similar chronically hypoxemic patients, manifest partially irreversible structural disarrangement subventricular...

Abstract Background The glial cell line‐derived neurotrophic factor has a potent neuroprotective action on mesencephalic dopamine neurons, which are progressively lost in Parkinson's disease. Intrastriatal administration of this is promising therapy for Glial naturally produced restricted cerebral regions, such as the striatum, septum, and thalamus; however, its effects adult brain remain under debate. Objectives We sought to clarify physiologic role endogenous survival catecholaminergic...

Administration of recombinant glial cell line-derived neurotrophic factor into the putamen has been tested in preclinical and clinical studies to evaluate its neuroprotective effects on progressive dopaminergic neuronal degeneration that characterizes Parkinson's disease. However, intracerebral infusion is a challenging therapeutic strategy, with numerous potential technical medical limitations. Most these limitations could be avoided if production endogenous increased. Glial naturally...